Stomach Cancer Secondary to Hematologic Diseases

PURPOSE: Patients with hematologic diseases such as chronic myeloid leukemia (CML) or chronic lymphoid leukemia (CLL) are known to have an increased chance of acquiring a secondary neoplasm. Stomach cancer is one of the most common malignant diseases in Korea, and we investigated whether the incidence of secondary stomach cancer in patients with a hematologic disease increases, in order to determine if a more intensive screening program for detecting secondary gastric cancer was required. We also investigated the safety of performing a gastrectomy in hematologic disease patients. MATERIALS AND METHODS: From 1992 to 2006, the medical records of 8376 patients diagnosed with one of the six common hematologic diseases were reviewed. RESULTS: Nine secondary stomach cancers were found among the 8376 patients during the 15-year observation period. No surgical-related complications occurred, and there was no recurrence of stomach cancer if detected early. CONCLUSION: It seems that a more intensive screening program for detecting secondary gastric cancer in hematologic disease patients is not required, and surgery is not risky in these patients.

The Changes in the Serum RANKL and OPG levels after Bone Marrow Transplantation: Association with Bone Mineral Metabolism / 대한내분비학회지

BACKGROUND: The loss of bone mass is usually detected after bone marrow transplantation(BMT), particularly during the early post-transplant period. We recently reported that enhanced bone resorption following BMT was related to both the steroid dose and increase in IL-6. It was also suggested damage of the marrow microenvironment due to myeloablation and changes in bone growth factors contribute to post-BMT bone loss. Recently, the interactions of OPG and RANKL have been reported to be crucial in osteoclastogenesis and therefore in bone homeostasis. There are few data on the changes in RANKL/OPG status during the post-BMT period. This study investigated the changes in the levels of RANKL and OPG during the post-BMT period, and also assessed whether the changes in these cytokine levels actually influenced bone turnover and post-BMT bone loss. METHODS: We prospectively investigated 110 patients undergoing allogenic BMT and analyzed 36 (32.4+/-1.3 years, 17 men and 19 women) where DEXA was performed before and 1 year after the BMT. The serum bone turnover marker levels were measured before and 1, 2, 3, 4 and 12 wks, 6 Ms, and 1 yr after the BMT. The serum sRANKL and OPG levels were measured in all patients before and 1, 3 and 12 wks after the BMT. RESULTS: The mean bone losses in the lumbar spine and total proximal femur, which were calculated as the percent change from the baseline to 1 yr, were 5.2(P<0.01) and 11.6%(P<0.01), respectively. The mean serum ICTP, a bone resorption marker, increased progressively until 3 and 6 months after the BMT, but decreased gradually thereafter, reaching the basal values after 1 year. The serum osteocalcin levels decreased progressively until 3 wks after the BMT, then increased transiently at 3 and 6 Ms, but returned to the basal level by 1 yr. The serum sRANKL and OPG levels had increased significantly by weeks 1 and 3 compared with the baseline(P<0.01), but decreased at 3 months. The sRANKL/OPG ratio increased progressively until 3 weeks, but then decreased to the basal values. During the observation period, the percent changes from the baseline in the serum RANKL levels and RANKL/OPG ratio showed positive correlations with the percent changes from the baseline serum ICTP levels. Patients with higher RANKL levels and RANKL/OPG ratio during the early post-BMT period lost more bone mass at the lumbar spine. CONCLUSION: In conclusion, dynamic changes in the sRANKL and OPG levels were observed during the immediate post-BMT period, which were related to a decrease in bone formation and loss of L-spine BMD during the year following the BMT. Taken together, these results suggest that increased sRANKL levels and sRANKL/OPG ratios could be involved in a negative balance in bone metabolism following BMT.

Chronic Cutaneous Graft versus Host Disease: Clinicopathologic study / 대한피부과학회지

BACKGROUND: Chronic graft-versus-host disease(GVHD) is a major cause of morbidity and mortality in long-term survivors of bone marrow transplantation, an increasingly used therapeutic option for hematological disorders. Cutaneous manifestations are frequently the presenting feature; therefore, the dermatologist needs to be aware of the wide spectrum of chronic cutaneous GVHD, enabling early diagnosis and management. OBJECTIVE: We investigated the clinical and histological features of chronic cutaneous GVHD in recipients receiving allogenic BMT. METHODS: On the basis of the patients' charts, photographs and biopsy specimens, we investigated the occurring interval, clinical manifestations and histological characteristics of chronic cutaneous GVHD in 37 patients from January 1, 1996 through December 31, 2000. RESULTS AND CONCLUSION: 1. The chronic cutaneous GVHD was preceded by the acute form of GVHD in 56.7% of patients, and occurred as an extension(18.9%) of acute GVHD, after a disease-free interval(37.8%), or with no precedent(43.2%). The disease usually developed at a mean 251days after transplant. 2. The chronic cutaneous GVHD mainly presented as maculopapular(37.8%), lichenoid(37.8%), or sclerodermoid(13.5%) patterns. 3. Histologically, 35.1% of biopsy specimens showed characteristic acute GVHR-like change, 40.5% showed lichen planus-like, and 13.5% was scleroderma-like histology. Lichen planus-like feature mixed with scleroderma-like was 2.7%, and 8.1 % was non-specific. 4. Appearing after day 100, the acute GVHD other than chronic GVHD was detected in some cases, and the lichenoid rash of chronic GVHD in one case was observed as early as day 60. 6. Our opinions are that the time of occurrence is not a reliable parameter for the clinical picture of GVHD and histologic parameters do not absolutely separate between acute and chronic GVHD as defined by days after BMT. 7. Mortality rate was 21 % in our cases.

The Effects of Aging on the Proliferation and Differentiation of Osteoblasts from Human Mesenchymal Stem Cells / 대한내분비학회지

BACKGROUND: Osteoblasts originate from osteoprogenitor cells in bone marrow stroma, termed mesenchymal stem cells (MSCs) or bone marrow stromal cells. Each MSC forms colonies (colony forming units-fibroblasts [CFU-Fs]) when cultured ex vivo. There are some reports about the age-related changes of the number and osteogenic potential of osteoprogenitor cells, but any relationship has not been clearly established in humans. In this study, we counted MSCs using CFU-Fs count and examined the proliferative capacity and differentiation potential of osteoprogenitor cells. Finally, we analyzed how these parameters varied with donor age. METHODS: Bone marrow was obtained from the iliac crest of young (n=6, 27.2+/-8.6 years old) and old (n=10, 57.4+/-6.7 years old) healthy donors. Mononuclear cells, including MSCs, were isolated and cultured in osteogenic medium. In primary culture, we compared the colony-forming efficiency of MSCs between the two groups and determined the matrix calcification. When primary culture showed near confluence, the cells were subcultured. Alkaline phosphatase activity, osteocalcinexpression by RT-PCR and proliferative potential by MTT assay were examined by the time course of secondary culture. RESULTS: At the 15th day of primary culture, the mean number of CFU-Fs was significantly higher in the younger donors (young: 148.3+/-28.9, old: 54.3+/-9.1, p=0.02) and the mean size of CFU-Fs was also larger in the younger donors than the older donors. However, matrix calcification was not different between the two groups (young: 103.6+/-50.6, old: 114.0+/-56.5, p=NS). In secondary culture, alkaline phosphatase activities were significantly lower in the older donors. The younger donors showed peak alkaline phosphatase activity at day 10, while the older donors didn't showed a remarkable peak (young: 935.5+/-115.0U/mg, old: 578.4+/-115.7U/mg, p<0.05). Total cell number as a proliferative index increased progressively during the secondary culture and a significantly greater cell number was noted in the younger donors. Osteocalcin expression was generally upregulated in the younger donors, but this was not statistically significant. CONCLUSION: Our study shows that the number of osteoprogenitor cells is decreased during aging and that the proliferative capacity and differentiation potential of osteoprogenitor cells seem to be reduced during aging.

The Skeletal Site-Differential Changes in Bone Mineral Density Following Bone Marrow Transplantation: 3-Year Prospective Study

Loss of bone mass is usually detected after bone marrow transplantation (BMT) during the early post-transplant period. However, little is known about the long-term effects of BMT on bone metabolism. We have prospectively investigated 11 patients undergoing BMT. Bone mineral density (BMD) was measured before BMT, and 1, 2, and 3 yr after BMT. Serum markers of bone turnover were serially measured before BMT and 1, 2, 3, 4, and 12 weeks, 6 months, and 1 yr after BMT. The mean change in the lumbar spine (L2-4) BMD, calculated as the percent change from the baseline to the level at 1, 2, and 3 yr was -4.7% (NS), -1.1% (NS), and +6.4% (p<0.05), respectively. The mean change in the total proximal femur BMD from the baseline to the level at 1, 2, and 3 yr was -8.5% (p<0.01), -8.7% (p<0.05) and -5.6% (p<0.05), respectively. In summary, there was little decline in lumbar BMD at 1 yr following BMT and gradual recovery until 3 yr. In contrast, femoral BMD decreased much more than the lumbar area at 1 yr and did not recover until 3 yr. The mechanism of skeletal site-selective differences in the changes of BMD needs to be elucidated.

Circulating IL-8 and IL-10 in Euthyroid Sick Syndromes following Bone Marrow Transplantation

It is generally agreed that euthyroid sick syndromes (ESS) are associated with an increased production of cytokines. However, there has been scarce data on the relationship thyroid hormone changes and cytokines among the patients undergoing bone marrow transplantation (BMT). Because interleukin-8 (IL-8) has been identified as a potent proinflammatory and interleukin-10 (IL-10) as an antiinflammatory cytokine, we studied the relation between thyroid hormone parameters and these cytokines following BMT. We studied 80 patients undergoing allogeneic BMT. Serum T3 decreased to nadir at post-BMT 3 weeks. Serum T4 was the lowest at the post-BMT 3 months. Serum TSH sharply decreased to nadir at 1 week and gradually recovered. Serum free T4 significantly increased during 3 weeks and then returned to basal level. Mean levels of serum IL-8 significantly increased at 1 week after BMT. Mean levels of serum IL-10 significantly increased until 4 weeks after BMT. No significant correlation was found between serum thyroid hormone parameters and cytokines (IL-8, IL-10) after adjusting steroid doses during the entire study period. In conclusion, ESS developed frequently following allogeneic BMT and cytokine levels were increased in post-BMT patients. However, no significant correlation was found between serum thyroid hormone parameters and these cytokines.

The Changes of Serum Growth Factors after Hematopoietic Stem Cell Transplantation: Impact on Bone Mineral Metabolism / 대한내분비학회지

BACKGROUND: A loss of bone mass is usually detected after a bone marrow transplantation (BMT), especially during the early post-transplant period. We recently reported that enhanced bone resorption following a BMT was related to both the steroid dose and the increase in IL-6. We also suggested damage to the marrow stromal microenvironment, by myoablation, partly explains the impaired bone formation following a BMT. It is well known that some growth factors play important role in bone growth and osteogenesis. However, the pathogenetic role of bone growth factors in post-BMT bone loss is unknown and data on the changes in the growth factors, in accordance with bone turnover markers and bone mineral density (BMD) changes are scarce. We investigated changes in bone growth factors such as IGF-I (Insulin-like growth factor-I), fibroblast growth factor-2 (FGF-2) and Macrophage colony stimulating factor (M-CSF), during the post-BMT period, and assessed whether the growth factor changes influenced the bone turnover and post-BMT bone loss. The present study is the first prospective study to describe the changes in bone growth factors following a BMT. METHODS: We prospectively investigated 110 patients undergoing a BMT, and analyzed 36 patients (32.4+/-1.3 years, 17 men and 19 women) whose BMDs were measured before, and 1 year after, the BMT. The serum biochemical markers of bone turnover were measured before, 1, 2, 3 and 4 weeks, 3 and 6 months, and 1 year, after the BMT. The serum FGF-2, IGF-I and M-CSF levels were measured before and 1 and 3 weeks, and 3 months after the BMT. The correlation between the changes of growth factors and various bone parameters was analyzed. RESULTS: The mean bone losses in the lumbar spine and total proximal femur, calculated as the percentage change from the baseline to the level at 1 year, were 5.2 (p<0.05) and 11.6% (p<0.01), respectively. The serum type I carboxyterminal telopeptide (ICTP), a bone resorption marker, increased progressively until 6 months after the BMT, but thereafter decreased, to the base value after 1 year. Serum osteocalcin, a bone formation marker, decreased progressively, until 3 weeks after the BMT but then increased transiently, and finally returned to the base level at 1 year. The serum IGF-I and FGF-2 also decreased progressively until 3 weeks and 1 week after the BMT, respectively, then increased to the base values at 3 months. The serum M-CSF increased briskly at 1 week post-BMT, then decreased to the base level. There were positive correlations between the percentage changes from the baseline proximal femur BMD and the IGF-I levels 3 weeks and 3 months (r=0.52, p<0.01, r=0.41, p<0.05) post BMT. A Significant correlation was found between the IGF-I and osteocalcin levels pre-BMT, and 3 weeks after the BMT. Another positive correlation was found between the M-CSF and the ICTP levels at 3 weeks post BMT (r=0.54, p<0.05). CONCLUSION: In conclusion, there were significant changes in the serum IGF-I, FGF-2 and M-CSF levels in the immediate post-BMT period, which were related to a decrease in bone formation and loss in the proximal femoral BMD during the year following the BMT

The Changes of Cytokines and Bone Turnover Markers after Bone Marrow Transplantation / 대한내분비학회지

BACKGROUND: Loss of bone mass is usually detected after BMT. The causes of bone loss are related with gonadal dysfunction and immunosuppressants. Cytokines, especially IL-6, play an important role in the pathogenesis of postmenopausal osteoporosis. However, the pathogenetic role of cytokines in post-BMT bone loss is unknown and data on the changes of cytokines in accordance with bone turnover markers are scarce. The aim of this study is to assess the relationship of bone turnover markers and cytokines of peripheral blood and bone marrow before and after allogeneic BMT. METHODS: This prospective study included two analyses. The first was a study of 46 BMT recipients, examining the relationship between bone turnover markers and cytokines of serum which were measured before and 1, 2, 3, 4 week and 3 months after BMT. The second was a study of 14 BMT patients, measuring bone marrow plasma cytokines such as IL-6 and TNF-alpha at post-BMT 3 week and bone turnover marker at the same time to assess the relationship between two parameters. RESULTS: Serum ICTP, bone resorption marker, increased progressively until 4 weeks (peak) after BMT and then decreased thereafter. Serum osteocalcin, bone formation marker, decreased progressively until 3 weeks after BMT and then increased thereafter. There was positive correlation between serum ICTP and bone marrow IL-6 levels at the post-BMT 3 week with a statistical significance, but the correlation between bone turnover markers and bone marrow TNF-alpha or peripheral blood cytokines was not found. CONCLUSION: Our data suggest that the progressive increase of bone resorption after BMT is related with the increase of bone marrow IL-6, which is a potent stimulator of bone resorption in vivo.

The Nonthyroidal Illness Syndrome: Prognostic Value and Circulating Cytokines after Allogeneic Bone Marrow Transplantation / 대한내분비학회지

BACKGROUND: Alteration of thyroid hormone parameters are frequently observed in sick patients and commonly known as nonthyroidal illness syndrome(NTIS) or euthyroid sick syndrome(ESS). NTIS is seen in starvation, surgery, severe illness, and also bone marrow transplantation(BMT). The degree of reduction in thyroid hormone parameters correlated with the severity of NTIS and might predict the prognosis of underlying illness. Recently, particular attention is focused on the role of cytokines in developing the NTIS. This prospective study was designed to assess the relationship of serum thyroid hormone parameters and serum cytokine levels before and in the short-term follow-up after allogeneic BMT in order to predict patients outcome. METHODS: Included 80 patients that were mainly leukemia and severe aplastic anemia. Serum thyroid hormone parameters and serum cytokine levels were measured before and 7, 14, 21, 28 days and 3, and 6 months after BMT. RESULTS: Near-all patients experienced significant decrease of thyroid hormone levels and also significant increase of cytokine levels after BMT. After post-BMT 3 weeks, the serum cytokine levels were negatively correlated with the serum T3 and T4 levels, but not with the serum TSH levels. The patients treated with high-dose steroid or total-body irradiation tended to show lower levels of TSH and more delayed recovery compared to non-treated patients. The patients died after BMT represented generally lower levels of all thyroid hormone parameters than survival patients during entire follow-up period. CONCLUSION: Development of NTIS is associated with higher probability of fatal outcome after BMT and has prognostic relationship in this group of patients. Increased levels of cytokines, especially IL-6 and TNF-alpha, are often found in post-BMT NTIS patients and correlated with the changes in the levels of thyroid hormone parameters.

The Effect of Bone Marrow Transplantation on Bone Mineral Metabolism: 2 - Year Prospective Study / 대한내분비학회지

BACKGROUND: Loss of bone mass is usually detected after bone marrow transplantation (BMT), especially during the early post-transplant period. But little is known about the long-term effects of BMT on bone mineral metabolism. METHODS: We have investigated prospectively 12 patients undergoing BMT (4 autologous, 8 allogeneic) for hematologic diseases (8 leukemia, 3 SAA, 1 MDS). Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones and bone turnover markers (osteocalcin and ICTP) were measured. The samples were collected before BMT and 1, 2, 3, 4, and 12 weeks, 6 months and 1, 2 years thereafter. Bone mineral density (BMD) was measured with DEXA (Dual Energy X-ray Absorptiometry) before BMT, 1 year and 2 year after BMT. In patients with amenorrbea, hormone replacement therapy was started from around 1 year after BMT RESULTS: 1. The mean bone loss in the lumbar spine, calculated as the percent change from the baseline to the level at 1 year and 2 year was 7.3% and 1.9%, respectively. The mean bone loss in the total proximal femur from the baseline to the level at 1 year and 2 year was 8.0% and 8.3% respectively. 2. The serum ICTP increased progressively until four weeks after BMT. Thereafter, it decreased gradually to reach basal values after one year and thereafter no more change until 2 year. Serum osteocalcin decreased progressively until three weeks after BMT. After that, it increased and reached basal values after 3 months. Osteocalcin increased at 6 month transiently but thereafter, it decreased to the level of slightly above basal value at 2 year. 3. Patients who were treated with TBI or pateints with GVHD had a tendency of lower BMD at l year and 2 year after BMT than those of patients without TBI or GVHD. 4. Eight out of nine women went into a menopausal state immediately after BMT and remained amenorrhea, evidenced by high gonadotropins and low estradiol levels. In contrast to women, gonadotropins and testosterone levels were not changed significantly in men after BMT. CONCLUSION: The rapid impairment of bone formation and the increase in bone resorption, as shown by the biochemical markers in this study, might play a role in bone loss after BMT. The efficacy of HRT for the correction of hypogonadism and bone loss was evidenced by 2 year BMD which was much more increased compared to 1 year BMD, especially in vertebra.

The Effect of Hematopoietic Stem Cell Transplantation in the Origin and the Osteoblastic Differentiation of the Human Bone Marrow Stromal Cell / 대한내분비학회지

BACKGROUND: Bone marrow transplantation is the treatment of choice for patients with certain- hematological malignancies, many of whom will survive many years thereafter. Bone disease is a potential longterm complication. But, little is known about the effects of bone marrow transplantation on bone. METHODS: In this study, bone marrow was obtained from healthy donor and transplant recipients. Then mononuclear cells including marrow stromal cells were isolated and cultured. At near confluence, bone marrow stromal cells were subcultured. Thereafter alkaline phosphatase activities of each group were measured by time course of secondary culture. We also analysed the origin of marrow stromal cells by the polymerase chain reaction using YNZ 22 minisatellite probe. RESULTS: l. Cells cultured in our system showed the characteristics of marrow stromal cells differentiated to osteoblasts. They were in fibroblast-like spindle shape and positive to alkaline pbosphatase histochemistry and Von Kossa histochemistry in secondary cultures. 2. The time required for the near confluence in the primary culture was 15 days and 22.9 days on the average in healthy donors and transplant recipients, respectively (p=0.003). 3. In secondary cultures, healthy donors and transplant recipients showed peak alkaline phosphatase activity at 10 days and 17 days, respectively (p=0.031). Alkaline phosphatase activity was lower in BMT recipients than in healthy donors during the whole period of secondary cultures. 4. In polymerase chain reaction analysis using YNZ 22 minisatellite probe, bone marrow stromal cells were of recipient origin. CONCLUSION: Recipient-derived bone marrow stromal cells may be damaged secondary to the effect of chemotherapy, glucocorticoid & total body irradiation which have given before bone marrow transplantation. So it may affect the differentiation of bone marrow stromal cells into the osteoblasts.

Immunophenotyping of Normal Human Bone Marrow by Flow Cytometric Analysis / 대한혈액학회지

BACKGROUND: By development of monoclonal antibodies (MoABs) directed against hematopoietic cells, flow cytometric analysis of bone marrow has become commonplace in clinical hematology laboratories and has a major role in evaluation of lymphohematopoietic malignancies. However, little information about antigen expressions and distribution of normal human bone marrow cells has been published. Therefore, we analysed the immunophenotype of the normal human bone marrow cells to get a normal baseline data for flow cytometric analysis. METHODS: The bone marrow aspirates of 20 healthy donors of allogeneic bone marrow transplantation were analysed using flow cytometry (Becton-Dickinson Co, USA). Seven gated region (R) were set using the forward vs. right angle light scatter (FSC/SSC) cytogram and the percentages of positive cells against 17 monoclonal antibodies were identified in these gated regions by dual parameter flow cytometry. RESULTS: The proportion of total CD45+ cells was 87.57+/-12.82% (mean+/-1SD, n=20) and CD45- (nucleated erythrocytes) cells was 12.43+/-12.82% of all nucleated bone marrow cells. T cells were more numerous than B cells in total gates (P=.0001). T helper/inducer cells (Th) to T suppressor/cytotoxic cells (Ts) ratio was 1.38+/-0.53 and CD4+ cells were distributed in larger size and higher SSC fractions in FSC/SSC cytogram than CD8+ cells (P=.0001). While CD4+, 8+ cells were rarely existed, CD10+ cells were 17.63+/-11.43% of all nucleated bone marrow cells and they mainly distributed in granulocytic fractions. Lymphocytes represent 60% of all lymphogate cells and T cells were mostly mature cells. CD10+ cells and CD34+ cells in the R1 (lymphogate) were 4.37+/-3.07% and 1.78+/-1.25%, respectively. The total CD34+ cells represent 0.88+/-0.5% of all nucleated bone marrow cells and 65% of them were CD34+CD33+ cells. CONCLUSION: These results indicate each subpopulation of normal bone marrow reveals different regional expression from morphological estimation and these normal expressions should be considered in flow cytometric analysis of hematologic disorders.

Effect of All - trans Retinoic Acid ( ATRA ) on the Remission Induction and Coaguloyathy in Acute Promyelocytic Leukemia ( APL ) / 대한내과학회지

OBJECTIVES: APL, which characteristically shows t(15:17), accompanies fatal coagulopathy during remission induction with systemic chemotherapy alone. ATRA, a derivative of vitamin A, can differentiate APL cells as well as HL-60 cells in vitro and induce higher rate of complete remission(CR). Hence, we assessed the effect of ATRA on remission induction and coagulopathy in APL patients. METHODS: (1) 42 patients diagnosed histologically in St. mary's hospital from June 1991 to June 1994 were included. (2) We compared the CR rate, the time required for restoration of derranged coagulation profiles, and the amount of coagulation factors including platelets among the chemotherapy group (control) and ATRA group. RESULTS: 1) There was no difference in CR rate between the control group and ATRA group [84.2%(16 out of 19) vs 87.0%(20 out of 23), p>0.05)] and also no difference between two subgroups of ATRA [ATRA with chemotherapy; 83.3%(10 out of 12) vs ATRA without chemotherapy; 90.9%(10 out of 11), p>0.05] 2) In the ATRA group, the CR rate of newly diagnosed patients was 82.4%(14 out of 17). The first relapsed patients (4) and the second (2) were all achieved CR. 3) The mean duration of coagulopathy, time to normalization of PT, aPTT, FDP, fibrinogen level, was 12.0+/-10.4, 11.1+/-10.2, 16.5+/-9.3, 15.4+/-10.2 days after chemotherapy alone and 4.5+/-4.4, 3.7+/-3.7, 8.9+/-6.1, 8.1+/-6.5 days in the ATRA group(p<0.05). The amount of fresh frozen plasma used in the ATRA group for the purpose of correction of coagulopathy were significantly lower than the control group(p<0.05). The incidence of profound coagulopathy during the remission induction treatment in the ATRA group was significantly lower than the control group[40% (8 out of 20) vs 96.7%(13 out of 15), p

Immunosuppressants induced reversible posterior dominant emcephalopathy-A capillary leak syndrome

BACKGROUNDS: Recently, the cases with transient neurologic deficit and brain MRI abnormalities similar to hypertensive encephalopathy or eclampsia were reported in the organ transplanted patients, during the administration of cyclosporine with the hypothesis as "capillary lack syndrome". But in addition to cyclosporine, other immunosuppressive agents as cytabine and ant-lymphocyte globulin(ALG) may induce similar transient neurologic manifestations such headache, seizure, altered mental state and change of signal intensities in brain MRI. METHODS AND CASES: 11 patients who had suffered form hematologic disorder were included in the study. The patients were presented with a reversible transient neurologic manifestations and brain MRI abnormalities during administration of various immunosuppressant,. We analysed neourologic symptoms and signs, anatomic localizations and laboratory findings. RESULTS: The underlying hematologic disorder were severe aplastic anemia acute lymphocyte leukemia, multiple myeloma, chronic myelocytic leukemia and acute myelocytic leukemia. The cyclosporine was prescribed in six. ALG in three, idarubicin in two and prednisolone in one patient. The accompanied neurologic symptoms and sign were seizure(11/11), visual disturbance or cortical blindness(5/11) and mental status change(3/11). All the symptoms were spontaneously improved by conservative management. The insidious increase on blood pressure, hepato-renal impairment, sepsis, and hepatopathy were noted in some cases just before and after the neurologic manifestation. The ESR was elevated in all examined cases and the cholesterol level was normal. Serum cyclosporine was elevated in 2/6 cases. They showed typical MRI findings which were high signal intensity an T2WI and iso- to low signal intensity on TIWI with blunding of cortical sulci and with no enhancement. The involved lesions were the parieto-occipital area, frontal lobe, temporal lobe, and basal ganglia in series. One patient showed a petechial hemorrhage in the occipital area on both CT and MRI. In six cases, follow-up MRI showed nearly complete resolution of the lesions correlated with the clinical symptoms. CONCLUSION: We can't explain the exact mechanisms of the neurologic complication of immunosuppressants, but the characterstics of transient neurologic deficits and the corresponding reversible brain image are similar to those of hypertensive encephalopathy or eclampsia. It is suggested that the mechanism of clinical syndrome maybe a capiliary leak due to the cytokine-induced vasculopathy but future studies are warranted.

A Clinical Study of chronic Cutaneous GVHD / 대한피부과학회지

BACKGROUND: With progressive improvement in the fraction of long-term surviviors, chronic GVHD has emerged as a increasingly frequent complication of allogenic bone marrow transplantation. Except for a few case reports, there has been no clinical study of chronic cutaneous GVHD in Korea so far. OBJECTIVE: In the present study we planned to investigate the clinical characteristics of chronic cutaneous GVHD and to compare the clinical manifestation and incidence of chronic cutaneous GVHD in Korea with previous reports in U.S.A. and Europe. METHODS: On the basis of the patients' charts and the records of bone marrow transplantation, we investigated the incidence of chronic cutaneous GVHD in Korean leukemia patients and studied the clinical manifestations of chronic cutaneous GVHD ocurring in 16 patients whose diagnosis was confirmed by histopathologic findings of skin biopsy. We also analysed whether total body irrdiation before bone marrow transplantation, GVHD prophylaxis and presence of preceding acute GVHD affected chronic cutaneous GVHD. RESULTS: 1. The incidence in chronic cutaneous GVHD in Korea was lower than that in Caucasian countries. 2. The onset was milder than that in Caucasians. 3. The clinical manifestation was earlier than that in Caucasians. 4. The relationship between the GVHD prophylaxis and incidence chronic cutaneous GVHD was not significant. 5. The incidence of chronic cutaneous GVHD in the presence of preceding acute GVHD was higher than in cases with no preceding acute GVHD. CONCLUSION: We speculate that the low incidence of chronic cutaneous GVHD and clinical characteristics differing from the reports in the U.S.A. and Europe might be unassociated with irradiation, GVHD prophylaxis or the presence of preceding acute GVHD but maybe related to differences in genetic background.

Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia / 대한치료방사선과학회지

Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6fractions/3days (6 patients) or 1320 cGy/8 fractions/4days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase.

Total Body Irradiation Technique: Basic Data Measurements and In Vivo Dosimetry / 대한치료방사선과학회지

This paper describes the basic date measurements for total body irradiation with 6 Mv photon beam including compensators designs. The technique uses bilateral opposing field with tissue compensators for the head, neck, lungs, and legs from the hip to toes. In vivo dosimetry was carried out for determining absorbed dose at various regions in 7 patients using diode detectors (MULTIDOSE, Model 9310, MULTIDATA Co., USA). As a results, the dose uniformity of+/-3.5%(generally, within+/-10%) can be achieved with our total body irradiation technique.

Five cases of cytomegalovirus infection detected by in situ hybridization and antigenemia assay

We report five cases of cytomegalovirus infection in immunocompromised patients which were detected by either cytomegalovirus antigenemia assay or in situ hybridization. Four cases had leukemia and the other had chronic renal failure. All the three BMT recipients suffered from GvHD. Interestingly, there was an unique case of CMV disease without a history of BMT, which reminded us that CMV could attack immunocompromised patients who had not undergone transplantation, too. Four out of five cases died. We think that cytomegalovirus infection or disease should not be regarded as a minor problem in post-transplantation infection in Korea.

Prognostic factors in patients with acute myelogenous leukemia(AML) who achieve primary complete remission / 대한암학회지

No abstract available.

A case of meningoencephalitis due to streptococcus pneumoniae in a patients with chronic graft-versus-host disease after allogeneic bone marrow transplantation / 감염

No abstract available.